In the brain of Alzheimer's patient many insoluble spots (senile plaque) are found, which is formed by extraneuronal accumulation of a peptide called amyloid β protein comprised of about 40 amino acids. Neuronal death caused by the senile plaque is considered to develop Alzheimer's Disease and an enhancer of amyloid β protein decomposition or vaccine of amyloid β protein etc. are extensively studied as a remedy for Alzheimer's Disease.
Secretase is an enzyme producing amyloid β protein by intracellular cleavage of a protein called amyloid β protein precursor (APP). An enzyme playing a role for producing an N-terminal of the amyloid β protein is called BACE1 (beta-site APP-cleaving enzyme) and an inhibitor of the BACE1, which will reduce production of amyloid β protein, could be a remedy for treating Alzheimer's disease.
Patent literature 1 discloses a compound with a chemical structure similar to that of the compound of the present invention, having an inhibitory activity of NO synthetase and effective for treating dementia.
Patent literature 2-5 and non-patent literature 1-2 disclose compounds with a chemical structure similar to those of the compound of the present invention, and describe that each compound is useful as an anti-hypotensive agent, morphine-like analgesic or tranquilizer, intermediate of a therapeutic agent, NPYY5 antagonist, analgesic and the like.
Patent literatures 6-14 disclose BACE-1 inhibitors having a chemical structure different from that of the compound of the present invention. Also, patent literature 15 discloses a BACE-1 inhibitor.    Patent literature 1: WO 96/014842 Pamphlet    Patent literature 2: U.S. Pat. No. 3,235,551    Patent literature 3: U.S. Pat. No. 3,227,713    Patent literature 4: JP H09-067355    Patent literature 5: WO 2005/111031 Pamphlet    Patent literature 6: WO 02/96897 Pamphlet    Patent literature 7: WO 04/043916 Pamphlet    Patent literature 8: WO 2005/058311 Pamphlet    Patent literature 9: WO 2005/097767 Pamphlet    Patent literature 10: WO 2006/041404 Pamphlet    Patent literature 11: WO 2006/041405 Pamphlet    Patent literature 12: US 2007/0004786A    Patent literature 13: US 2007/0004730A    Patent literature 14: US 2007/27199A    Patent literature 15: WO 2007/049532 Pamphlet    Non-patent literature 1: Journal of Heterocyclic Chemistry, 14, 717-723 (1977)    Non-patent literature 2: Journal of Organic Chemistry, 33 (8), 3126-3132 (1968).